title: Glucose transporters and ATP-gated K+ (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells.
abstract: Although the heteromeric combination of type 1 taste receptors 2 and 3 (T1r2 + T1r3) is well established as the major receptor for sugars and noncaloric sweeteners, there is also evidence of T1r-independent sweet taste in mice, particularly so for sugars. Before the molecular cloning of the T1rs, it had been proposed that sweet taste detection depended on (a) activation of sugar-gated cation channels and/or (b) sugar binding to G protein-coupled receptors to initiate second-messenger cascades. By either mechanism, sugars would elicit depolarization of sweet-responsive taste cells, which would transmit their signal to gustatory afferents. We examined the nature of T1r-independent sweet taste; our starting point was to determine if taste cells express glucose transporters (GLUTs) and metabolic sensors that serve as sugar sensors in other tissues. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we determined that several GLUTs (GLUT2, GLUT4, GLUT8, and GLUT9), a sodium-glucose cotransporter (SGLT1), and two components of the ATP-gated K(+) (K(ATP)) metabolic sensor [sulfonylurea receptor (SUR) 1 and potassium inwardly rectifying channel (Kir) 6.1] were expressed selectively in taste cells. Consistent with a role in sweet taste, GLUT4, SGLT1, and SUR1 were expressed preferentially in T1r3-positive taste cells. Electrophysiological recording determined that nearly 20% of the total outward current of mouse fungiform taste cells was composed of K(ATP) channels. Because the overwhelming majority of T1r3-expressing taste cells also express SUR1, and vice versa, it is likely that K(ATP) channels constitute a major portion of K(+) channels in the T1r3 subset of taste cells. Taste cell-expressed glucose sensors and K(ATP) may serve as mediators of the T1r-independent sweet taste of sugars.
authors.affiliation: Monell Chemical Senses Center, Philadelphia, PA 19104-3308, USA.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Yee
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Sukumaran
authors.forename: Ramana
authors.initials: R
authors.lastname: Kotha
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Gilbertson
authors.forename: Robert F
authors.initials: RF
authors.lastname: Margolskee
mesh_terms: D000818:Animals; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D005905:Glyburide / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000378:metabolism; D054086:KATP Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013549:Sweetening Agents / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism; D013649:Taste / Q000502:physiology; D013650:Taste Buds / Q000166:cytology*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D007004:Hypoglycemic Agents; D054086:KATP Channels; D043562:Receptors, G-Protein-Coupled; C494209:Snap25 protein, mouse; D013549:Sweetening Agents; D050825:Synaptosomal-Associated Protein 25; C431926:taste receptors, type 1; D005905:Glyburide